Alkyl halides, super hydrogen production and the pathogenesis of pneumatosis cystoides coli.
OBJECTIVE
The colons of patients with pneumatosis cystoides coli produce excessive H2. Exposure to alkyl halides could explain this. Six consecutive patients who had pneumatosis cystoides coli while taking chloral hydrate (1-5+ g/day) are reported. Patients 2 and 3 were investigated after they had ceased chloral hydrate treatment. One produced methane, the other did not. (Pneumatosis cystoides coli patients are non-methanogenic according to the literature.) Both had overnight fasting breath H2 of less than 10 ppm. A literature review disclosed just one patient who was using chloral at the time of diagnosed pneumatosis cystoides coli, but an epidemic of the disease in workers exposed to trichloroethylene.


METHODS
(i) In vitro experiments with human faeces: chloral or closely related alkyl halides were added to anaerobic faecal cultures derived from four methane-producing and three non-methanogenic human subjects. H2 and CH4 gases were measured. (ii) In vivo animal experiment: chloral hydrate was added to drinking water of four Wistar rats, and faecal H2 compared with control rats.


RESULTS
Alkyl halides increased H2 up to 900 times in methanogenic and 10 times in non-methanogenic faecal cultures. The Ki of chloral was 0.2 mM. Methanogenesis was inhibited in concert with the increase in net H2. In the rat experiment, chloral hydrate increased H2 10 times, but did not cause pneumatosis.


CONCLUSIONS
Chloral and trichloroethylene are alkyl halides chemically similar to chloroform, a potent inhibitor of H2 consumption by methanogens and acetogens. These bacteria are the most important H2-consuming species in the colon. It is postulated that exposure to these alkyl halides increases net H2 production, which sets the scene for "counterperfusion supersaturation" and the formation of gas cysts. In recent times, very low prescribing rates for chloral have caused primary pneumatosis cystoides to become extremely rare. As with primary pneumatosis, secondary pneumatosis cystoides, which occurs if there is small bowel bacterial overgrowth distal to a proximally located gut obstruction, is predicted by counterperfusion supersaturation. "Inherent unsaturation" due to metabolism of O2 is a safety factor, which could explain why gas bubbles do not form more often in tissue with high H2 tension.
Florin
T H
TH
Department of Medicine (UQ), Mater Adult Hospital, South Brisbane, Australia.
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002697:Chloral Hydrate / Q000009:adverse effects* / Q000378:metabolism; D003108:Colonic Diseases / Q000139:chemically induced* / Q000378:metabolism; D003903:Deuterium / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000378:metabolism; D008297:Male; D008697:Methane / Q000378:metabolism; D008875:Middle Aged; D011006:Pneumatosis Cystoides Intestinalis / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D006993:Hypnotics and Sedatives; D002697:Chloral Hydrate; D006859:Hydrogen; D003903:Deuterium; D008697:Methane